With improvements in nutrition and advances in veterinary medicine has come an increase in lifespan of animals. An increase in an animal's lifespan, however, comes at a cost, for example older animals become less active and gain weight causing stress on joints leading to pain and inflammation, and older animals are more prone to degenerative diseases such as Alzheimer's disease, Amyotrophic Lateral Sclerosis (ALS), Osteoarthritis, Atherosclerosis, Cancer, Charcot Marie Tooth Disease (CMT), Chronic Obstructive Pulmonary Disease (COPD), etc. All or some of which require long-term medication, for example for pain relief or for treatment of inflammation.
Approximately 20% of all pet dogs suffer from osteoarthritis (OA) at some stage and require constant treatment for pain and inflammation. Of old dogs (over seven years old), up to 50% suffer from joint pains that are treated with continuous anti-inflammatory medication, sometimes combined with surgical intervention. OA is also common among old cats (cats are commonly referred to as being “older” when they have reached the age of eight to ten years). The number of cats and dogs suffering from OA is increasing, because they live longer and because overweight and obesity among pets are increasing. Most frequently used non-steroidal anti-inflammatory drugs (NSAIDs) are meloxicam and carprofen. Animal owners are responsible for daily administration of these drugs and their success in administration contributes greatly in receiving and maintaining the therapeutic drug level in the animal's plasma and consequently managing the pain and inflammation. Success factors in administration are the owner's commitment and the animal's submission to treatment. Cats, especially, are difficult to administer to orally.
Oral administration presents a number of challenges. Many active pharmaceutical ingredients are bitter in taste and although many masking substances have been developed these have been found not entirely effective and in the main, animals, e.g. companion animals, find oral medications unpleasant in flavour and prefer not to ingest them.
Consequently, at least a part of the oral dosage can be ejected from the animal's mouth and intestinal system through drooling and the therapeutic level in plasma is not reached. The animal can also resist administration so successfully that no drug enters the mouth and intestinal system, leading to lowered plasma level of the drug and an increased feeling of pain e.g. caused by inflammation.
Conversely, it is also known that an animal, e.g. a dog, has actually liked the flavour of the drug and managed to steal extra doses resulting in undesirably high plasma levels of the drug leading to various unpleasant side effects.
Various studies show, however, that the biggest reason for dosing failure is owner behaviour: forgetting to administer the drug, lack of concern, wanting to avoid own stress, and stressing the animal with administration being typical excuses.
At a growing rate, owners are also buying medication from internet vendors, leading to fewer vet visits and thus to a lack of professional evaluations of disease progress. This results in at least ill-adjusted dosing and an increased risk of side-effects in the animal.
Furthermore, tablets and chewing tablets allow only for rough dosage adjustment for animals of different sizes, especially among dogs. For example, tablets/chewing tablets are typically manufactured for three different dog weight groups and in one group the weight can vary almost 100% (for example dogs 5.1 to 10 kg). Sometimes owners end up dividing tablets to adjust doses, which in case of small tablet sizes can lead to major differences in the amount of active ingredients administered.
Various means have been developed to overcome the burden of daily administration of medication to animals. For example, Mavacoxib, a veterinary drug for the treatment of pain and inflammation in dogs with degenerative joint disease has such a long elimination time that a single oral administration is enough to maintain a therapeutic level for one month liberating owners from daily administration. However, this can become problematic if the animal does not tolerate the drug: there is no means to remove the active ingredient that has already entered systemic circulation.
For the efficient administration of drugs to animals novel delivery modes must be developed. In order to deliver a drug and maintain therapeutic plasma levels of the drug in an animal, a shift away from conventional oral administration is required.
US 2011/0123596 discloses a silica sol material for the production of biodegradable and/or absorbable silica gel materials containing an active ingredient, such as an NSAID. The silica gel materials disclosed therein are suitable for topical administration in the treatment of wounds suffered by humans.
WO 2014/207304 discloses a silica hydrogel composite obtainable by mixing silica particles, comprising an encapsulating agent, with a silica sol, wherein obtained hydrogel composite is shear-thinning, and a use thereof for an injectable flowing or extrudable formulation.
U.S. Pat. No. 7,897,166 relates to a spun silica fibre containing an active pharmaceutical ingredient. The fibres are spun directly from a sol that has been aged to increase its viscosity.
US 2014/057996 relates to a method of producing a flowing silica composition having a biologically active agent mixed into the silica composition. The flowing silica composition is administered to humans and animals.
As mentioned above, commonly used NSAIDs in animal care comprise the active pharmaceutical ingredients (API) meloxicam and carprofen.
Carprofen is available in tablet form, e.g. in the US in 25 mg, 75 mg and 100 mg, and in the UK in 20 mg, 50 mg and 100 mg tablets. In the US, carprofen is also available as an injectable. The usual dosage is e.g. 4.4 mg/kg per day in dogs.
Meloxicam is available in various forms. In the US, for example, meloxicam is available in tablets including 7.5 and 15 mg meloxicam for cats and dogs, in oral suspension form for cats and dogs, 0.5 and 1.5 mg/ml, and horses 15 mg/ml. Meloxicam is further available via injection (intravenous and subcutaneous) form for dogs and cats, (with boxed warning for use in cats), 2 and 5 mg/ml. Further injection concentrations of 5 and 50 mg/ml are available for production animals including cattle, sheep and pigs. Chewing tablets are available for dogs in doses of 1 and 2.5 mg and an oral paste comprising 50 mg/g meloxicam is available for horses. Further, an oral spray is available for dogs, said spray delivering a dose of meloxicam of 0.25, 0.50, or 1.075 mg/spray.
Typically, meloxicam is delivered in a starting dose of 0.2 mg/kg body mass of the patient on the first day, followed by a maintenance dose of 0.1 or 0.05 mg/kg body mass of the patient on each following day.
These delivery methods, and dosage sizes and dosage regimens present the same problems as mentioned above, e.g. rough dosage, lack of owner compliance, difficulty in administration. A further problem that is presented by carprofen and meloxicam is that they are both practically insoluble in water. This means that in injectable form a vector in which each of these APIs is soluble is required. In practical terms this means that ethanol is invariably used. Ethanol is known in some cases to cause the unpleasant side effect of cutaneous necrosis.